{"doi":"10.7554/elife.73055","title":"Allosteric cooperation in β-lactam binding to a non-classical transpeptidase","abstract":"L,D -transpeptidase function predominates in atypical 3 → 3 transpeptide networking of peptidoglycan (PG) layer in Mycobacterium tuberculosis . Prior studies of L,D -transpeptidases have identified only the catalytic site that binds to peptide moiety of the PG substrate or β-lactam antibiotics. This insight was leveraged to develop mechanism of its activity and inhibition by β-lactams. Here, we report identification of an allosteric site at a distance of 21 Å from the catalytic site that binds the sugar moiety of PG substrates (hereafter referred to as the S-pocket). This site also binds a second β-lactam molecule and influences binding at the catalytic site. We provide evidence that two β-lactam molecules bind co-operatively to this enzyme, one non-covalently at the S-pocket and one covalently at the catalytic site. This dual β-lactam-binding phenomenon is previously unknown and is an observation that may offer novel approaches for the structure-based design of new drugs against M. tuberculosis .","journal":"eLife","year":2022,"id":277663,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":949278,"name":"Sanmati Dugad","orcid":"0000-0002-1890-1734","position":1,"is_corresponding":false},{"id":949279,"name":"Varsha Chauhan","orcid":"0000-0002-1234-1932","position":2,"is_corresponding":false},{"id":323266,"name":"Shubbir Ahmed","orcid":"0000-0003-1655-6735","position":3,"is_corresponding":false},{"id":949280,"name":"Kunal Sharma","orcid":"0000-0002-7348-7978","position":4,"is_corresponding":false},{"id":949281,"name":"Sangita Kachhap","orcid":"0000-0003-2009-1782","position":5,"is_corresponding":false},{"id":949282,"name":"Rana Zaidi","orcid":"0000-0002-5911-143X","position":6,"is_corresponding":false},{"id":241544,"name":"William R. Bishai","orcid":"0000-0002-8734-4118","position":7,"is_corresponding":false},{"id":299601,"name":"Gyanu Lamichhane","orcid":"0000-0002-2214-0114","position":8,"is_corresponding":false},{"id":949283,"name":"Pankaj Kumar","orcid":"0000-0001-9163-3273","position":9,"is_corresponding":false},{"id":949277,"name":"Nazia Ahmad","orcid":"0000-0002-7419-7737","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T00:28:39.226969Z","pmid":"35475970","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}